Azithromycin, a recently introduced antibiotic, offers the potential advantages of short-course administration and lower toxicity compared to other macrolides. Approved for the treatment of mild pneumonia, this drug was investigated in a study of patients hospitalized for community-acquired pneumonia. In an open-labelled randomized study, oral azithromycin was compared with intravenous benzylpenicillin in patients suspected to have pneumococcal pneumonia. Azithromycin was also compared with erythromycin, both administered orally, in all other patients. Three hundred thirty-four patients with community-acquired pneumonia were hospitalized, 108 of whom were randomized; 104 could be evaluated. A need for intravenous therapy was the most common reason for exclusion. In the pneumococcal group, 35 patients received azithromycin and 29 benzylpenicillin. The clinical and radiological success rate achieved with azithromycin (83%) was considerably higher than that achieved with benzylpenicillin (66%), though the difference was not significant. In the non-pneumococcal group, 19 patients received azithromycin and 21 erythromycin; no differences in the success rate were found (79% and 76%, respectively). Eight patients on azithromycin had a blood culture positive for Streptococcus pneumoniae; in three of these patients therapy was changed. None of the five patients with pneumococcal bacteraemia who received benzylpenicillin required a change in therapy. It is concluded that oral azithromycin, administered as short-course therapy, is an appropriate antibiotic for treating patients with community-acquired pneumonia. However, it is not yet certain that azithromycin is a good choice for patients with pneumococcal bacteraemia.

Elimination and absorption of orally administered cloxacillin (Orbenin) was studied in 11 patients on chronic intermittent haemodialysis and 11 healthy subjects. For the patients, the mean value of the elimination rate constant was 0.31 h^-1 (T ½ = 2¼ h). Haemodialysis had no detectable effect on the elimination rate. The value found for the normals (1.21 h^-1; T½ = 34 min) is in accordance with the data in the literature. The extrarenal elimination rate in normals corresponds with the total elimination rate in patients without kidney function. In 6 of our patients the mean value of the absorption after oral administration of 1 g was 61% of the administered dose. The reliability of the method used to determine absorption in anuric patients from serum concentrations was verified by experiments in healthy subjects in whom absorption could also be estimated, on the basis of renal excretion. Our method proved to be reliable if certain reservations are taken into account. On the basis of the data obtained, we consider it advisable to give the same dosages of cloxaciUin to anuric patients as to patients with normal kidney function.

Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).

According to Gibaldi et al. (1968, 1970), the higher serum concentrations of penicillins and cephaloridine reached after administration of probenecid are due not only to slower renal elimination but also to an altered distribution in the body. To determine whether probenecid has a direct effect on the distribution of cloxacillin, the elimination and distribution of cloxacillin was studied in six patients, five lacking kidney function and one with a partially impaired renal function, in the presence or absence of probenecid. No significant difference was found between the mean values of the volume of distribution of cloxacillin with and without probenecid (13.0 and 12.6 liters, respectively). Thus, the hypothesis of Gibaldi et al. could not be confirmed for cloxacillin in patients lacking kidney function. In spite of the absence of kidney function, the value of the elimination rate constant was significantly decreased in the presence of probenecid (from 0.326 to 0.263/h). This might be explained by a blockade by probenecid of the elimination of cloxacillin by the liver.

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